Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients

S. Terakura, M. Murata, T. Nishida, N. Emi, Yoshiki Akatsuka, Y. Morishima, Y. Kodera, T. Naoe

Research output: Contribution to journalArticle

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Abstract

Treatment-related mortality (TRM) is a major obstacle to successful allogeneic hematopoietic stem cell transplantation (HSCT). A variety of drugs are used in allogeneic HSCT, and a genetic polymorphism in metabolic enzymes could affect the metabolism of drugs and potentially influence TRM. Here, we focused attention on GSTM1 and GSTT1 enzymes, which metabolize chemotherapeutic agents, chemical carcinogens and by-products of oxidative stress and are absent from more than 50% of some populations. To assess the significance of homozygous GSTM1 and GSTT1 gene deletion in HSCT, we analyzed DNA from 373 patients with hematological disease and their HLA-identical unrelated bone marrow donors using PCR. Homozygous GSTM1 and GSTT1 gene deletions were observed in 56 and 45% of patients, respectively, and 57 and 46% of donors, respectively. There was no significant association between GSTT1 polymorphism and any outcome. However, a GSTM1-positive genotype in recipients was significantly associated with higher TRM and lower survival. These results suggest that a GSTM1-null genotype in recipients protects against TRM after allogeneic HSCT. Further studies are needed to elucidate a mechanism of increased risk for TRM in GSTM1-positive recipients.

Original languageEnglish
Pages (from-to)381-386
Number of pages6
JournalBone Marrow Transplantation
Volume37
Issue number4
DOIs
Publication statusPublished - 01-02-2006
Externally publishedYes

Fingerprint

Bone Marrow Transplantation
Hematopoietic Stem Cell Transplantation
Mortality
Gene Deletion
Genotype
Tissue Donors
Therapeutics
Hematologic Diseases
Genetic Polymorphisms
Enzymes
Pharmaceutical Preparations
Carcinogens
Oxidative Stress
Bone Marrow
Polymerase Chain Reaction
Survival
DNA
Population

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Terakura, S., Murata, M., Nishida, T., Emi, N., Akatsuka, Y., Morishima, Y., ... Naoe, T. (2006). Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients. Bone Marrow Transplantation, 37(4), 381-386. https://doi.org/10.1038/sj.bmt.1705257
Terakura, S. ; Murata, M. ; Nishida, T. ; Emi, N. ; Akatsuka, Yoshiki ; Morishima, Y. ; Kodera, Y. ; Naoe, T. / Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients. In: Bone Marrow Transplantation. 2006 ; Vol. 37, No. 4. pp. 381-386.
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Terakura, S, Murata, M, Nishida, T, Emi, N, Akatsuka, Y, Morishima, Y, Kodera, Y & Naoe, T 2006, 'Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients', Bone Marrow Transplantation, vol. 37, no. 4, pp. 381-386. https://doi.org/10.1038/sj.bmt.1705257

Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients. / Terakura, S.; Murata, M.; Nishida, T.; Emi, N.; Akatsuka, Yoshiki; Morishima, Y.; Kodera, Y.; Naoe, T.

In: Bone Marrow Transplantation, Vol. 37, No. 4, 01.02.2006, p. 381-386.

Research output: Contribution to journalArticle

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AU - Naoe, T.

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